Highly Cytokinergic IgE Antibodies and Autoimmune Mechanisms

© Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease http://e-aair.org Immediate type hypersensitivity reactions can occur after allergen exposure followed by allergen-specific IgE-FcεRI interactions on mast cells/basophils in sensitized subjects. In comparison, chronic allergic inflammation induced by Th1 responses can occur without exposure to environmental allergens; instead, an IgE-mediated response to autoallergens can activate Th1 cells, causing them to release pro-inflammatory cytokines. Kitaura et al. demonstrated that mast cells with sensitized IgE antibodies on their surface can display a wide spectrum of heterogeneity in their ability to induce cytokine production and secretion. The spectrum of IgE antibodies has two extremes: highly cytokinergic IgE antibodies that induce potent survival promotion, degranulation, cytokine production, and migration, and poorly cytokinergic IgE antibodies that release minimal amounts of cytokines. An article published in this issue demonstrated that human IgE antibodies as well as mouse IgE antibodies show heterogeneity. This is clinically relevant for two reasons. First, human IgE antibodies showed heterogeneity in cytokine production and second, highly cytokinergic IgE antibodies showed polyreactivity to autoantigens. This concept was tested in serum from atopic dermatitis patients, since some of these patients have high levels of ssDNA(or dsDNA-) or β-galactosidase-reactive IgE antibodies with high levels of histamine releasing factor-reactive IgE antibodies. Most atopic dermatitis patients had very high total IgE levels in their serum, and polyclonal IgE antibodies detected in serum from these patients enhanced the survival of and cytokine production by mast cells. These findings suggest that an autoimmune mechanism is a part of chronic inflammation in a subset of atopic dermatitis patients, although they did not screen serum specific IgE to potential auto-antigens related with skin inflammation. Further studies investigating the mechanisms how polycytokinergic IgE antibodies reacting various kinds of autoantigens can activate other inflammatory cells and mast cells in various phenotypes of atopic dermatitis are essential. Furthermore, the IgE antibodies exhibited polyreactivity to the autoantigens tested in this study. Some Highly Cytokinergic IgE Antibodies and Autoimmune Mechanisms